Shared functional specialization in transformer-based language models and the human brain.

When processing language, the brain is thought to deploy specialized computations to construct meaning from complex linguistic structures. Recently, artificial neural networks based on the Transformer architecture have revolutionized the field of natural language processing. Transformers integrate contextual information across words via structured circuit computations. Prior work has focused on the internal representations ("embeddings") generated by these circuits. In this paper, we instead analyze the circuit computations directly: we deconstruct these computations into the functionally-specialized "transformations" that integrate contextual information across words. Using functional MRI data acquired while participants listened to naturalistic stories, we first verify that the transformations account for considerable variance in brain activity across the cortical language network. We then demonstrate that the emergent computations performed by individual, functionally-specialized "attention heads" differentially predict brain activity in specific cortical regions. These heads fall along gradients corresponding to different layers and context lengths in a low-dimensional cortical space.

E-cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.

The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial-mesenchymal transition (EMT), which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.

Characterisation of extracellular vesicles in baculovirus infection of Spodoptera frugiperda cells.

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an enveloped DNA virus of the Baculoviridae family. This baculovirus is widely exploited for the biological control of insect pest species and as an expression platform to produce recombinant proteins in insect cells. Extracellular vesicles (EVs) are secreted by all cells and are involved in key roles in many biological processes through their cargo consisting of proteins, RNA or DNA. In viral infections, EVs have been found to transfer both viral and cellular cargo that can elicit either a pro- or antiviral response in recipient cells. Here, small EVs (sEVs) released by Spodoptera frugiperda (Sf) insect cells were characterised for the first time. Using S. frugiperda (SfC1B5) cells stably expressing the baculovirus gp64, the viral envelope protein GP64 was shown to be incorporated into sEVs. Sf9 cells were also transfected with a bacmid AcMNPV genome lacking p6.9 (AcΔP6.9) to prevent budded virus production. The protein content of sEVs from both mock- and AcΔP6.9-transfected cells were analysed by mass spectrometry. In addition to GP64, viral proteins Ac-F, ME-53 and viral ubiquitin were identified, as well as many host proteins including TSG101-which may be useful as a protein marker for sEVs.

Genetic characterization of the prion protein gene in camels (Camelus) with comments on the evolutionary history of prion disease in Cetartiodactyla.

Transmissible spongiform encephalopathies (TSEs) are a fatal neurogenerative disease that include Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE), and several others as well as the recently described camel prion disease (CPD). CPD originally was documented in 3.1% of camels examined during an antemortem slaughterhouse inspection in the Ouargla region of Algeria. Of three individuals confirmed for CPD, two were sequenced for the exon 3 of the prion protein gene (PRNP) and were identical to sequences previously reported for Camelus dromedarius. Given that other TSEs, such as BSE, are known to be capable of cross-species transmission and that there is household consumption of meat and milk from Camelus, regulations to ensure camel and human health should be a One Health priority in exporting countries. Although the interspecies transmissibility of CPD currently is unknown, genotypic characterization of Camelus PRNP may be used for predictability of predisposition and potential susceptibility to CPD. Herein, eight breeds of dromedary camels from a previous genetic (mitochondrial DNA and microsatellites) and morphological study were genotyped for PRNP and compared to genotypes from CPD-positive Algerian camels. Sequence data from PRNP indicated that Ethiopian camels possessed 100% sequence identity to CPD-positive camels from Algeria. In addition, the camel PRNP genotype is unique compared to other members of the Orders Cetartiodactyla and Perissodactyla and provides an in-depth phylogenetic analysis of families within Cetartiodactyla and Perissodactyla that was used to infer the evolutionary history of the PRNP gene.

Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Oncology Nursing Society (ONS) standards for antineoplastic therapy administration safety in adult and pediatric oncology and highlight current standards for antineoplastic therapy for adult and pediatric populations with various routes of administration and location. METHODS: ASCO and ONS convened a multidisciplinary Expert Panel with representation of multiple organizations to conduct literature reviews and add to the standards as needed. The evidence base was combined with the opinion of the ASCO-ONS Expert Panel to develop antineoplastic safety standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance. In addition, the standards have added a fourth verification. STANDARDS: Standards are provided for which health care organizations and those involved in all aspects of patient care can safely deliver antineoplastic therapy, increase the quality of care, and reduce medical errors.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease : A Systematic Review and Retrospective Individual Participant-Level Meta-analysis of Clinical Trials.

BACKGROUND: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. PURPOSE: To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death. DATA SOURCES: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. STUDY SELECTION: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. DATA EXTRACTION: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. DATA SYNTHESIS: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). LIMITATION: Individual participant-level data for hyperkalemia or acute kidney injury were not available. CONCLUSION: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. PRIMARY FUNDING SOURCE: National Institutes of Health. (PROSPERO: CRD42022307589).

Electrodiagnostic subtyping in Guillain-Barré syndrome patients in the International Guillain-Barré Outcome Study.

BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

Utility of noninvasive electrocardiographic imaging in the localization of nonpulmonary vein triggers of atrial fibrillation determined by pacing common trigger sites.

INTRODUCTION: Identifying the origin of nonpulmonary vein atrial fibrillation (AF) triggers (NPVTs) after pulmonary vein isolation (PVI) can be challenging. We aimed to determine if noninvasive electrocardiographic imaging (ECGi) could localize pacing from common NPVT sites. ECGi combines measured body surface potentials with heart-torso geometry acquired from computed tomography (CT) to generate an activation map. METHODS: In 12 patients with AF undergoing first time ablation, the ECGi vest was fitted for preprocedural CT scan and worn during the procedure. After PVI, we performed steady-state pacing from 15 typical anatomic NPVT sites at a cycle length of 700-800 ms. We co-registered the invasive anatomic map with the CT-based ECGi epicardial activation map to compare ECGi predicted to true pacing origin. RESULTS: In the study cohort (67% male, 58% persistent AF, and 67% with left atrial dilation), 148 (82%) pacing sites had both capture and adequate anatomy acquired from the three-dimensional mapping system to co-register with ECGi activation map. Median distance between true pacing sites and point of earliest epicardial activation derived from the ECGi maps for all sites was 17 mm (interquartile range, 10-22 mm). Assuming paced sites treated as regions with a radius of 2.5 cm, the earliest activation site on ECGi map falls within the region with 94% accuracy. CONCLUSION: ECGi can approximate the origin of paced beats from common NPVT sites to within a median distance of 17 mm. A rapidly identified region may then be the focus of more detailed catheter-based mapping techniques to facilitate successful localization and ablation of NPVTs.

Single-neuron analysis of aging-associated changes in learning reveals impairments in transcriptional plasticity.

The molecular mechanisms underlying age-related declines in learning and long-term memory are still not fully understood. To address this gap, our study focused on investigating the transcriptional landscape of a singularly identified motor neuron L7 in Aplysia, which is pivotal in a specific type of nonassociative learning known as sensitization of the siphon-withdraw reflex. Employing total RNAseq analysis on a single isolated L7 motor neuron after short-term or long-term sensitization (LTS) training of Aplysia at 8, 10, and 12 months (representing mature, late mature, and senescent stages), we uncovered aberrant changes in transcriptional plasticity during the aging process. Our findings specifically highlight changes in the expression of messenger RNAs (mRNAs) that encode transcription factors, translation regulators, RNA methylation participants, and contributors to cytoskeletal rearrangements during learning and long noncoding RNAs (lncRNAs). Furthermore, our comparative gene expression analysis identified distinct transcriptional alterations in two other neurons, namely the motor neuron L11 and the giant cholinergic neuron R2, whose roles in LTS are not yet fully elucidated. Taken together, our analyses underscore cell type-specific impairments in the expression of key components related to learning and memory within the transcriptome as organisms age, shedding light on the complex molecular mechanisms driving cognitive decline during aging.

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age.

BACKGROUND: Dupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents. METHODS: In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically. RESULTS: In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B. CONCLUSIONS: Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.).

Effects of medical cannabis use on physical and psychiatric symptoms across the day among older adults.

INTRODUCTION: Older adults are increasingly using medical cannabis (MC). It is unclear if therapeutic effects increase problematic use patterns. The current study addresses this issue by examining symptom trajectories across the day and using trajectories to predict problematic use. METHODS: One-hundred six older adults (age range 55-74) who endorsed medical conditions approved for treatment using MC were recruited online. Participants received six text messages/day to assess momentary symptoms for 15 days. RESULTS: Participants provided 5,156 momentary assessments across 1,106 use days. Symptom trajectories were examined across the day. There was a decline in all symptoms following use. Negative affect, pain, and nausea evinced momentary negative reinforcement associations with cannabis intoxication. Momentary negative reinforcement was associated with adverse cannabis outcomes. Declines in post-use trauma symptoms and momentary negative reinforcement effects for negative affect were both associated with cannabis use disorder symptoms. DISCUSSION: These data suggest that MC may be effective in reducing common symptom clusters. However, the negative reinforcing effect (i.e., the link between use and symptom relief at the event level) may complicate the therapeutic nature (i.e., symptom reduction). Identifying interventions to maximize benefits while minimizing costs may increase the efficacy and safety of MC in older adults.

Air Pollution and Adverse Cardiovascular Events After Coronary Artery Bypass Grafting: A 10-Year Nationwide Study.

Background: Increased particulate matter <2.5 µm (PM2.5) air pollution is associated with adverse cardiovascular outcomes. However, its impact on patients with prior coronary artery bypass grafting (CABG) is unknown. Objectives: The purpose of this study was to evaluate the association between major adverse cardiovascular events (MACE) (defined as myocardial infarction, stroke, or cardiovascular death) and air pollution after CABG. Methods: We linked 26,403 U.S. veterans who underwent CABG (2010-2019) nationally with average annual ambient PM2.5 estimates using residential address. Over a 5-year median follow-up period, we identified MACE and fit a multivariable Cox proportional hazard model to determine the risk of MACE as per PM2.5 exposure. We also estimated the absolute potential reduction in PM2.5 attributable MACE simulating a hypothetical PM2.5 lowered to the revised World Health Organization standard of 5 µg/m3. Results: The observed median PM2.5 exposure was 7.9 µg/m3 (IQR: 7.0-8.9 µg/m3; 95% of patients were exposed to PM2.5 above 5 µg/m3). Increased PM2.5 exposure was associated with a higher 10-year MACE rate (first tertile 38% vs third tertile 45%; P < 0.001). Adjusting for demographic, racial, and clinical characteristics, a 10 µg/m3 increase in PM2.5 resulted in 27% relative risk for MACE (HR: 1.27, 95% CI: 1.10-1.46; P < 0.001). Currently, 10% of total MACE is attributable to PM2.5 exposure. Reducing maximum PM2.5 to 5 µg/m3 could result in a 7% absolute reduction in 10-year MACE rates. Conclusions: In this large nationwide CABG cohort, ambient PM2.5 air pollution was strongly associated with adverse 10-year cardiovascular outcomes. Reducing levels to World Health Organization-recommended standards would result in a substantial risk reduction at the population level.

COVID-19 vaccine related anxiety partially mediates the association between COVID-19 related anxiety and student adjustment to college during the pandemic.

The COVID-19 pandemic caused severe disruptions in living and learning to millions of college students. Here we investigated using mediation analysis two dimensions of anxiety that were specific to the pandemic - COVID-19 related anxiety and COVID-19 vaccine anxiety - to evaluate their relationship to college adjustment during the pandemic. Using cross-sectional survey data across three semester waves (Spring 2021, Fall 2021, and Spring 2022) we probed whether anxiety functioned as a challenge or hindrance stressor on adjustment. We found that although anxiety decreased in both COVID-19 dimensions across semesters, student adjustment to college remained consistently low. Our mediation analysis revealed that both COVID-19 related anxiety and COVID-19 vaccine-related anxiety functioned as challenge stressors, elevating academic, social, personal-emotional, and institutional adjustment during the pandemic. We discuss the role of positive COVID impacts on college adjustment, including enhanced social support.

Association Between Cognitive Trajectories and Subsequent Health Status, Depressive Symptoms, and Mortality Among Older Adults in the United States: Findings From a Nationally Representative Study.

BACKGROUND: Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort. METHODS: Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes. RESULTS: Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates. CONCLUSIONS: Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes.

A review of calcium and phosphorus requirement estimates for gestating and lactating sows.

Calcium (Ca) and phosphorus (P) are minerals involved in biological functions and essential structural components of the skeleton. The body tightly regulates Ca and P to maintain homeostasis. Maternal needs for Ca and P increase during gestation and lactation to support conceptus growth and milk synthesis. Litter size and litter average daily gain (ADG) have a large effect on Ca and P requirements for sows because as they increase, the requirements increase due to a greater need from the sow. The objective of this review was to summarize published literature on Ca and P requirements in gestating and lactating sows derived from empirical data and factorial models. A total of nine empirical studies and seven factorial models were reviewed for determining the Ca and P requirements in gestation. For lactation, there were six empirical studies and seven factorial models reviewed. Empirical studies determined requirements based on the observed effect of Ca and P on bone mineralization, sow and litter performance, and milk characteristics. Factorial models generated equations to estimate Ca and P requirements using the main components of maintenance, fetal and placental growth, and maternal retention in gestation. The main components for factorial equations in lactation include maintenance and milk production. In gestation, the standardized total tract digestible phosphorus (STTD P) requirement estimates from empirical studies range from 5.4 to 9.5 g/d with total Ca ranging from 12.9 to 18.6 g/d to maximize bone measurements or performance criteria. According to the factorial models, the requirements increase throughout gestation to meet the needs of the growing fetuses and range from 7.6 to 10.6 g/d and 18.4 to 38.2 g/d of STTD P and total Ca, respectively, on day 114 of gestation for parity 1 sows. During lactation, STTD P requirement estimates from empirical studies ranged from 8.5 to 22.1 g/d and total Ca ranged from 21.2 to 50.4 g/d. For the lactation factorial models, STTD P requirements ranged from 14.2 to 25.1 g/d for STTD P and 28.4 to 55.6 g/d for total Ca for parity 1 sows with a litter size of 15 pigs. The large variation in requirement estimates makes it difficult to define Ca and P requirements; however, a minimum level of 6.0 and 22.1 g/d of STTD P during gestation and lactation, respectively, appears to be adequate to meet basal requirements. The limited data and high variation indicate a need for future research evaluating Ca and P requirements for gestating and lactating sows.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Language matters for biodiversity.

Language is central to the way people learn about the natural world. A salient concern of the biodiversity conservation arena has been to understand how language can be employed by scientists to communicate knowledge to nonexpert audiences and build ecological literacy. The use of analogy and narrative by scientists are prominent techniques. In this article, we consider how these two modes of language-based reasoning extend into ordinary conversational language use by the public, specifically when articulating everyday understanding and experiences of biodiversity. Drawing on a process of public engagement in a UK woodland environment, a typological framework based on principles of analogical and narrative reasoning is developed to characterize the precise character of processes of everyday biodiversity sense making. The implications of the framework are discussed in the context of future biodiversity research, particularly its participatory and educational dimensions.

The Role of Dietary Intake in the Weight Loss Outcomes of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: A Systematic Review and Meta-analysis.

The relationship between postoperative dietary intake and weight loss after bariatric surgery remains unclear. We performed a systematic review and meta-analysis of studies published between January 2000 and May 2023, reporting weight loss outcomes, and dietary intake before and after Roux-en-Y gastric bypass and sleeve gastrectomy. A total of 42 studies were included. There was no detectable difference in dietary intake between the two procedures. Roux-en-Y gastric bypass induced an average decrease in energy intake of 886 kcal/day at 12-month post-surgery; however, there was no correlation between daily energy intake and weight loss. These findings show a substantial reduction of energy intake in the first year after bariatric surgery but do not support a link between lower energy intake and greater weight loss.